Regulation of NF-E2 activity in erythroleukemia cell differentiation

Tadashi Nagai, Kazuhiko Igarashi, Jun Etsu Akasaka, Kazumichi Furuyama, Hiroyoshi Fujita, Norio Hayashi, Masayuki Yamamoto, Shigeru Sassa

Research output: Contribution to journalArticle

67 Citations (Scopus)

Abstract

The erythroid transcription factor NF-E2 is an obligate heterodimer composed of two different subunits (p45 and p18), each containing a basic region-leucine zipper DNA binding domain, and it plays a critical role in erythroid differentiation as an enhancer-binding protein for expression of the β-globin gene. We show here that dimethyl sulfoxide treatment of wild- type murine erythroleukemia cells, but not a mutant clone of dimethyl sulfoxide-resistant cells, increases NF-E2 activity significantly, which involves both up-regulation of DNA binding and transactivation activities. Both activities were reduced markedly by treatment of cells with 2- aminopurine but not by genistein. Activation of the Ras-Raf-MAP kinase signaling cascade increased NF-E2 activity significantly, but this was suppressed when MafK was overexpressed. Domain analysis revealed an activation domain in the NH2-terminal region of p45 and a suppression domain in the basic region-leucine zipper of MarK. These findings indicate that induction of NF-E2 activity is essential for erythroid differentiation of murine erythroleukemia cells, and serine/threonine phosphorylation may be involved in this process. In addition, they also suggest that a MafK homodimer can suppress transcription, not only by competition for the DNA binding site, but also by direct inhibition of transcription. Hence, MafK may function as an active transcription repressor.

Original languageEnglish
Pages (from-to)5358-5365
Number of pages8
JournalJournal of Biological Chemistry
Volume273
Issue number9
DOIs
Publication statusPublished - 1998 Feb 27
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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